FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival

Sunil Badve, Dmitry Turbin, Mangesh A. Thorat, Akira Morimiya, Torsten O. Nielsen, Charles M. Perou, Sandi Dunn, David G. Huntsman, Harikrishna Nakshatri

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of ∼50% of estrogen receptor α (ERα):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers. Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu. Results: FOXA1 expression (score >3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer - specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213). Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.

Original languageEnglish
Pages (from-to)4415-4421
Number of pages7
JournalClinical Cancer Research
Volume13
Issue number15
DOIs
StatePublished - Aug 1 2007

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Estrogen Receptors
Breast Neoplasms
Survival
Neoplasms
Progesterone Receptors
Forkhead Transcription Factors
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Genes
Estrogens
Multivariate Analysis
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival. / Badve, Sunil; Turbin, Dmitry; Thorat, Mangesh A.; Morimiya, Akira; Nielsen, Torsten O.; Perou, Charles M.; Dunn, Sandi; Huntsman, David G.; Nakshatri, Harikrishna.

In: Clinical Cancer Research, Vol. 13, No. 15, 01.08.2007, p. 4415-4421.

Research output: Contribution to journalArticle

Badve, S, Turbin, D, Thorat, MA, Morimiya, A, Nielsen, TO, Perou, CM, Dunn, S, Huntsman, DG & Nakshatri, H 2007, 'FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival', Clinical Cancer Research, vol. 13, no. 15, pp. 4415-4421. https://doi.org/10.1158/1078-0432.CCR-07-0122
Badve, Sunil ; Turbin, Dmitry ; Thorat, Mangesh A. ; Morimiya, Akira ; Nielsen, Torsten O. ; Perou, Charles M. ; Dunn, Sandi ; Huntsman, David G. ; Nakshatri, Harikrishna. / FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 15. pp. 4415-4421.
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abstract = "Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of ∼50{\%} of estrogen receptor α (ERα):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers. Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu. Results: FOXA1 expression (score >3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer - specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213). Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.",
author = "Sunil Badve and Dmitry Turbin and Thorat, {Mangesh A.} and Akira Morimiya and Nielsen, {Torsten O.} and Perou, {Charles M.} and Sandi Dunn and Huntsman, {David G.} and Harikrishna Nakshatri",
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T1 - FOXA1 expression in breast cancer - Correlation with luminal subtype A and survival

AU - Badve, Sunil

AU - Turbin, Dmitry

AU - Thorat, Mangesh A.

AU - Morimiya, Akira

AU - Nielsen, Torsten O.

AU - Perou, Charles M.

AU - Dunn, Sandi

AU - Huntsman, David G.

AU - Nakshatri, Harikrishna

PY - 2007/8/1

Y1 - 2007/8/1

N2 - Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of ∼50% of estrogen receptor α (ERα):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers. Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu. Results: FOXA1 expression (score >3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer - specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213). Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.

AB - Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of ∼50% of estrogen receptor α (ERα):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers. Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu. Results: FOXA1 expression (score >3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer - specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213). Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.

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